This proposal will perform a comprehensive prospective assessment of the characteristics of the vaso-occlusive pain experience in African-American children and adolescents with Sickle Cell Disease (SCD) to determine the factors that contribute to a poor response to analgesic therapy. Our hypothesis is that poor clinical responses to analgesic therapy are a multi-factorial event that include potential contributions from characteristics of the pain experience (pain intensity), from the pharmacologic therapy (altered drug clearance, bioavailability, or altered dose-response relationship), and from the patient's psychological attributes. In addition, we will also examine factors that contribute to the perceived necessity for utilization of hospital-based services by our patients and families with SCD for treatment of painful episodes. Our hypothesis is that this behavior can be predicted by a modified stress- psychological adjustment model. These studies are part of larger program that is determining the prevalence and etiology of hypoxia in SCD and its relationship with vaso-occlusive pain, and examining the role of lipoxygenase metabolites in mediating the effects of hypoxia on endothelial cell - red cell interactions. This proposal will be the first study to specifically characterize the pain intensity of both outpatient and hospital-treated painful episodes with a prospective design in a large population of children and adolescents with SCD. More importantly, this study will examine several other facets of the pain experience in these patients that have not been previously studied in any depth. We will conduct the first detailed study of the pharmacokinetiCs of intravenous and oral morphine and codeine in patients with SCD. We will also conduct a study of the pharmacodynamics of intravenous morphine by characterizing the dose response relationship for ventilatory response to CO2 , and PCA-mediated analgesia. Finally, we will examine the psychological and psychosocial attributes of patients who experience painful episodes, and characterize those factors that predict psychological adjustment, reported pain severity, or hospital service utilization. While each one of these studies could be done in isolation, the combination of these studies in the same patient population, on a prospective basis, will yield a wealth of comparative information that will allow us to assess the relative importance of a comprehensive set of biopsychosocial factors which predict clinical response to analgesic therapy for painful episodes, the most frequent and debilitating complication of SCD. With this knowledge, we will be better able to alleviate the pain and suffering of these patients, and improve their quality of life until definitive anti-sickling therapy becomes a part of our routine clinical practice for children and adolescents with SCD.